Implantable Medical Devices

ABSTRACT

An implantable medical system that comprises a gas unit for supplying gas that is essentially oxygen and at least one functional cells unit configured to receive oxygen from the gas unit so as to maintain the cells in a viable condition. The cells unit is flexible. Several embodiments are disclosed.

CROSS-REFERENCE TO THE RELATED APPLICATIONS

This application is a continuation relating to and claiming the benefitof commonly-owned, co-pending U.S. application Ser. No. 14/227,258entitled “IMPLANTABLE MEDICAL DEVICES,” filed Mar. 27, 2014, theentirety of which is incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates generally to implantable medical deviceshaving an oxygen reservoir and a flexible functional cells unitprotected from the host immune system.

BACKGROUND OF THE INVENTION

Several disorders arising from hyposecretion of one or more substancessuch as hormones are known. Among these are diabetes, Parkinson'sdisease, Alzheimer's disease, hypo- and hyper-tension, hypothyroidism,and various liver disorders. The hormone insulin, for example, isproduced by β-cells in the islets of Langerhans of the pancreas. Innormal individuals, insulin release is regulated so as to maintain bloodglucose levels in the range of about 70 to 110 milligrams per deciliter.In diabetics, insulin is either not produced at all (Type 1 diabetes),or the body cells do not properly respond to the insulin that isproduced (Type 2 diabetes). The result is elevated glucose levels in theblood.

Disorders arising from hyposecretion of a hormone are usually treated byadministration of the missing hormone. However, despite advances inunderstanding and treating many of these diseases, it is often notpossible to precisely regulate metabolism with exogenous hormones. Adiabetic patient, for example, is required to make several dailymeasurements of blood glucose levels and then inject an appropriateamount of insulin to bring the glucose levels to within the acceptablerange.

Organ transplantation is not a viable treatment today for most of thesedisorders for several reasons including rejection of a transplantedorgan by the immune system. Isolated cells may be implanted in the bodyafter being treated to prevent rejection e.g. by immunosuppression,radiation or encapsulation. The encapsulating material is selected so asto be biocompatible and to allow diffusion of small molecules betweenthe cells and the environment while shielding the cells fromimmunoglobulins and cells of the immune system. Encapsulated β-cells orislets of Langerhans (the tissue producing the insulin), for example,can be injected into the portal vein or embedded under the skin, in theabdominal cavity, or in other locations. The success of many cellulartransplants is compromised not only due to graft-host rejections, butalso on account of ischemic conditions generated by insufficient oxygensupply to the transplant. Following implantation of the cells, oxygen isprovided to the implanted cells from the body tissue (mainly viadiffusion), and in some cases, from vascular structures that form aroundthe transplanted cells with the help of angiogenic factors, e.g., VEGFand bFGF. However, the natural diffusion rate is too low to provide thecells with a sufficient amount of oxygen, especially inmacro-encapsulation and high density of the cells.

Oxygen is vital for the physiological processes and functionality of theimplanted cells. An insufficient supply of oxygen to the implantedcells, often leads to cell loss of functionality or death. Oxygenprovision is a vital component in sustaining transplanted cells.

Attempts are made to assure sufficient oxygen to the implanted cells.U.S. Pat. No. 7,892,222 entitled “Implantable Device”; to Vardi et al.,teaches an implantable device comprising a chamber for holdingfunctional cells and an oxygen generator for providing oxygen to thefunctional cells.

In one embodiment, the oxygen generator is described as comprisingphotosynthetic cells that convert carbon dioxide to oxygen whenilluminated. In another embodiment, the oxygen generator is described ascomprising electrodes that produce oxygen by electrolysis.

U.S. Pat. No. 8,012,500 to Rotem et al. describes apparatus including achamber, which is adapted to be implanted in a body of an individual,the chamber including functional cells and chlorophyll-containingelements comprising chlorophyll of an obligate photoautotroph.Typically, the chlorophyll-containing elements include intactphotosynthetic cells and/or isolated chloroplasts. Thechlorophyll-containing elements provide oxygen to the functional cellsand/or consume carbon dioxide produced by the functional cells.

U.S. Pat. No. 8,444,630 titled “Oxygen Supply for Cell Transplant andVascularization” to Rotem, et al. describes an apparatus including ahousing configured for insertion into a body of a patient; aphotosynthetic oxygen supply configured to supply oxygen; and functionalcells, coupled to the housing. The functional cells are adapted toreceive the oxygen and to secrete at least one factor that inducesvascularization in a vicinity of the housing when the housing is in thebody of the patient. Other embodiments are also described.

When no oxygen reservoir is present, configurations of the implants isdesired. An example is taught in U.S. Pat. No. 5,855,613 to Antanavichet al., entitles Retrievable Bioartificial Implants having DimensionsAllowing Rapid Diffusion of Oxygen and Rapid Biological Response toPhysiological Change. This patent describes bioartificial implants andmethods for their manufacture and use, particularly bioartificialpancreases. In particular, the implants may be thin sheets that enclosecells or tissue, may be completely biocompatible over extended periodsof time and may induce minimal fibrosis. The viability of thehigh-density-cell-containing thin sheets is achieved by nourishing thetissue or cells with sufficient oxygen supply. The device is completelyretrievable, and have dimensions allowing maintenance of optimal tissueviability through rapid diffusion of nutrients and oxygen and alsoallowing rapid secretion rate of insulin and/or other bioactive agentsin response to changing physiology. Implantations of living cells,tissue, drugs, medicines and/or enzymes, contained in the bioartificialimplants may be made to treat and/or prevent diseases.

SUMMARY OF THE INVENTION

The present invention relates generally to an implantable medical devicehaving a unit that comprises the transplanted cells protected from thehost immune system and oxygen unit that may be separated. One of themain objects of the embodiments described is to provide an amount offunctional cells such as Islets of Langerhans that is significantly highrelative to the devices that are taught in prior art documents. As anexample, for effective usage of such implanted medical device, theimplantation of 250,000 islets and more is needed. To minimize thevolume the system occupies, high density of the islets, cells or tissuesis required. In dense cells, oxygen may become the first limitingnutrient and therefore, it has to be continuously supplied at asufficient rate. It is an object in the described embodiments to providesystems having a reservoir of gas that can assure the viability andfunctionality of the implanted cells, tissue or islets.

Moreover, the cell unit is thin and physically flexible in order toincrease the comfort of the patient and reduce the body response to theimplant expected after implantation.

It is therefore provided, in accordance with one embodiment, animplantable medical system comprising:

a gas unit for supplying gas, wherein said gas comprises essentiallyoxygen;

at least one of a plurality of functional cells unit having a certaindegree of physical flexibility and configured to receive oxygen from thegas unit so as to maintain the functional cells in a viable condition.

Furthermore and in accordance with another preferred embodiment, thesystem further comprising at least one distributor configured todistribute the gas from said gas unit to said plurality of functionalcells unit.

Furthermore and in accordance with another preferred embodiment, saidgas unit is a pressurized reservoir of gas that can be replenishedthrough a subcutaneous implantable port and wherein said port isconfigured to receive gas through a needle adapted to penetrate saidreplenishing port through skin.

Furthermore and in accordance with another preferred embodiment, auni-directional valve is provided between the replenishing port and thepressurized reservoir to ensure gas is solely transferred from the portto the reservoir.

Furthermore and in accordance with another preferred embodiment, saidgas unit is an oxygen generator.

Furthermore and in accordance with another preferred embodiment, saidoxygen generator generates oxygen by hydrolysis and comprises a pair ofelectrodes and a power source.

Furthermore and in accordance with another preferred embodiment, thefunctional cells are selected from a group comprising islets ofLangerhans, adrenal cells, stem cells and genetic implantable cells.

Furthermore and in accordance with another preferred embodiment, saidfunctional cells unit has one dimension that is relatively longer thanother dimensions so as to render flexibility to the unit, and whereinthe unit is flexible enough so as to allow the unit to partially followthe natural movements of the body organs that are adjacent to the unit.

Furthermore and in accordance with another preferred embodiment, saidfunctional cells unit is in a shape of a disc having a thickness of 1-8mm and a diameter of 1-20 cm. Furthermore and in accordance with anotherpreferred embodiment, said functional cells unit comprises oppositepositioned compartments of substantially the same dimensions, bothcompartments are provided with a relatively high surface area facethrough which oxygen can diffuse and reach the functional cells insidethe unit.

Furthermore and in accordance with another preferred embodiment, thehigh surface area face is covered with a layer that facilitates transferof oxygen.

Furthermore and in accordance with another preferred embodiment, saidlayer is a silicone layer.

Furthermore and in accordance with another preferred embodiment, outersides of said functional cells unit is covered with another layerpermeable to nutrients and bio-materials that may be produced by thefunctional cells and impermeable to immunologic factors and oxygen.

Furthermore and in accordance with another preferred embodiment, saidcompartments are disc-like and are having a thickness of about 20-2,000μm.

Furthermore and in accordance with another preferred embodiment, thefunctional cells are embedded in a matrix within the unit.

Furthermore and in accordance with another preferred embodiment, saidmatrix is made of materials selected from a group that comprisesalginate, collagen, and combination thereof.

Furthermore and in accordance with another preferred embodiment, thefunctional cells in the cell unit are trapped within a porous structure.

Furthermore and in accordance with another preferred embodiment, saidfunctional cells unit comprises a plurality of subunits havingsubstantially large surface area that allows transfer of oxygen whereineach subunit is provided with functional cells embedded in a matrix.

Furthermore and in accordance with another preferred embodiment, saidsubunits are arranged similarly to an egg carton, wherein the diameterof each subunit is about 10-2,500 μm.

Furthermore and in accordance with another preferred embodiment, saidfunctional cells unit is provided with inner projections configured toallow the functional cells to be captured by.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is herein described, by way of example only, withreference to the accompanying drawings. With specific reference to thedrawings in detail, it is stressed that the particulars shown are by wayof example and for purposes of illustrative discussion of the preferredembodiments of the present invention only, and are presented in thecause of providing what is believed to be useful and readily understooddescription of the principles and conceptual aspects of the invention.In this regard, no attempt is made to show structural details of theinvention in more detail than is necessary for a fundamentalunderstanding of the invention, the description taken with the drawingsmaking apparent to those skilled in the art how the several forms of theinvention may be embodied in practice.

The invention is capable of other embodiments or of being practiced orcarried out in various ways. Also, it is to be understood that thephraseology and terminology employed herein is for the purpose ofdescription and should not be regarded as limiting.

In discussion of the various figures described herein below, likenumbers refer to like parts. The drawings are generally not to scale.For clarity, non-essential elements were omitted from some of thedrawings. Some optional parts were drawn using dashed lines.

FIG. 1 schematically depicts a medical system according to an exemplaryembodiment of the current invention.

FIG. 2a illustrates a system for controlled flow of gas from the gasunit to the cells unit incorporated in the system shown in FIG. 1, inaccordance with one embodiment.

FIG. 2b schematically shows the controlled release of gas in theexemplary embodiment.

FIG. 3 illustrates the port when replenished with gas from outside thebody in accordance with an exemplary embodiment.

FIG. 4 illustrates a gas unit incorporated with a port in accordancewith an exemplary embodiment.

FIG. 5 schematically depicts a medical system according to anotherexemplary embodiment of the current invention.

FIG. 6 illustrates a medical system according to yet another exemplaryembodiment provided with a plurality of functional cells unit.

FIG. 7a illustrates a functional cell unit according to a preferredembodiment.

FIG. 7b illustrates a compartment of a functional cell unit according toanother preferred embodiment.

FIG. 7c illustrates a compartment of a functional cell unit according toyet another preferred embodiment.

FIG. 7d illustrates a compartment of a functional cell unit according toyet another preferred embodiment.

FIG. 8 illustrates an oxygen distributor according to another preferredembodiment.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention relates generally to an implantable medicaldevices without immunosuppressive therapy and to an apparatus and methodin which oxygen is in constant availability to the transplanted cells,e.g., cells in transplanted pancreatic islets within the implantedmedical device.

Before explaining at least one embodiment of the invention in detail, itis to be understood that the invention is not limited in its applicationto the details of construction and the arrangement of the components setforth in the following description or illustrated in the drawings. Theinvention is capable of other embodiments or of being practiced orcarried out in various ways. Also, it is to be understood that thephraseology and terminology employed herein is for the purpose ofdescription and should not be regarded as limiting.

In discussion of the various figures described herein below, likenumbers refer to like parts.

The drawings are generally not to scale. Some optional parts were drawnusing dashed lines.

For clarity, non-essential elements were omitted from some of thedrawings.

FIG. 1 schematically depicts a medical system 20 according to anexemplary embodiment.

Medical system 10 is subcutaneously implanted beneath the skin 12 of apatient, relatively close to the skin. Medical system 10 comprises aunit 14 that accommodate the functional cells or functional tissue.Functional cells can be selected from a group of cells such as islets ofLangerhans, adrenal cells, stem cells and genetic implantable cells. Thefunctional cell unit 14 is configured in a coin-like shape thatmaintains the unit flexible enough so as to be able to adjust to themovements of the body and encounter minimal discomfort to the patient.

The physical flexibility of the unit is such that the unit followspartially the natural movements of the body organs that are adjacent toit. As an example, if the unit is adjacent to a muscle tissue, when thetissue is stretched, the unit should accommodate itself in partial or infull to the stretching movement. Moreover, one possible location fortransplants of such devices is beneath the skin in the abdomen area andthis area is susceptible to be leaned on, the unit should have theflexibility to adjust itself to the item that leans on it such as atable, when a person is sitting.

Preferable dimensions of a disc-like shaped unit 14 are 1-8 mm inthickness and a diameter of about 1-20 cm. It should be noted that anyother shape can be utilized as long as one of the dimensions of the unitis small relative to the others, rendering the desired flexibility tothe unit.

The implanted medical system 10 further comprises a gas unit 16. The gasunit 16 is preferably a pressurized reservoir that can be implantedwithin the body wherein the reservoir can also be flexible, but can alsobe stiff. Usually, it is preferable that the gas content will be about95% oxygen and 5% carbon dioxide, in any case, the gas comprisesessentially oxygen. The pressure range should be more than oneatmosphere (the environment pressure) and up to 100 atmospheres;however, the preferable range is between 1-10 atmospheres.

The gas unit 16 and the distributor 20 are fluidically connected througha gas tube 18. Gas (essentially oxygen) is transferred through tube 18from the gas unit to supply oxygen to the cells unit so as to maintainthe cells in viable condition. The pressure in the tube 18 shouldn'texceed about 1-3 atmospheres, where 1 atm is the ambient pressure. Thegas can be released into the functional cells unit 14 through an oxygendistributor 20. From the oxygen distributor, the gas diffuses to thefunctional cells as will be explained herein after.

The release of the gas from the gas unit 16 can be performed usingdifferent methods. One option is to install an electrical valve orelectrical gate. Another option is the use of special mechanical valve.

The gas within the gas unit 16 can be replenished through a gasreplenishing port 26. The port should be positioned in the vicinity ofthe skin 12. A one-direction valve 28 is positioned between the port 26and the gas unit 16 so as to ensure that all the gas being accumulatedwithin the gas unit 16 and a pressure above one atmosphere is maintainedwithin the gas unit. The gas can replenish by inserting a needle throughthe skin 12 of the patient and into the port 26 through a membrane,typically silicon-rubber that is provided in the port and placedadjacent the skin.

Reference is now made to FIG. 2a illustrates a system for controlledflow of gas incorporated in the system shown in FIG. 1. The electricalvalve can be a gas solenoid valve 22 made of parts that receiveelectrical impulses and then translate those impulses into mechanicalmovements that opens or closes the valve and controls the flow of gas tothe cells unit. Optionally, the gas solenoid valve's housing is providedwith a coil that sits inside and receives the electrical currents fromat least one sensor 24 that may be positioned in the oxygen distributor20 or in the vicinity of the functional cells. The sensor 24 senses theamount of oxygen in the distributor 20, as shown in FIG. 2 and operatesthe electric valve 22. When the level of oxygen in the distributor 20reaches a predetermined threshold (e.g. 300 mm Hg), the sensor 24 sendsan electrical signal to valve 22. The solenoid valve 22 then convertsthe electrical impulses received by the coil into mechanical partsinside the valve to open the valve and release an additional amount ofgas. This is repeated. The gas in the tank is dropping in steps whileafter a while and when the gas level approaches about one atmosphere,the ambient pressure; the gas in the gas unit 16 should be replenished.

Optionally, the pressure control can be performed by mechanical means inwhich a spring or pressure differences controls the transfer of gas fromthe gas unit 16 to the tube 18.

Optionally, a membrane can be placed between the gas unit 16 and thetube 18. In this case, a relatively continuous and steady flow of gas tothe functional cells in the cells unit 14 can be accomplished.

Optionally, pressure control can be performed by electrical gate openedin predetermined time intervals based, as an example, on the expectedconsumption of oxygen.

Optionally, the valve can be a mechanical valve that is operated basedon pressure differences between the gas unit 16 and the distributor 20.

Reference is now made to FIG. 3 illustrating the port when replenishedwith gas from outside the body in accordance with one embodiment. Aneedle 30 c is inserted through the skin 12 and into the port 26 througha membrane 30 (e.g. silicon rubber membrane) that is being punctured bythe needle 30 c. The needle is connected to a tube 29 c from which thegas is inserted in the needed pressure.

Optionally, the port 26 is incorporated within the gas unit 16, as shownin FIG. 4.

All components of the implanted medical system are made of materialsthat are biocompatible and are adapted to be accommodated within thebody of a patient for a relatively long period of time (e.g. years).

Alternatively, an oxygen generator can be employed in order to preventthe need to puncture the skin each time replenishment of gas is needed.The oxygen generator may be located separately from the functional cellsunit 14, or instead of the distributor 20. Reference is now made to FIG.5 schematically depicting a medical system according to anotherexemplary embodiment of the current invention. System 100 comprises thefunctional cells unit 14 and an oxygen distributor 20 that receivesoxygen from a chamber 32 that constantly delivers oxygen to thefunctional cells unit 14 so as to assure the cells are viable. Theoxygen generator comprises pair of electrodes 34A and 34B that arepreferably flexible and are positioned partially within the chamber 32.The electrodes are preferably made of a biocompatible material such ascarbon or platinum. The system further comprises a power source 38 and amicroprocessor 36. When an electrical potential is generated between theelectrodes 34A and 34B by the power source 38, hydrolysis of watermolecules is initiated and resulted in oxygen production. The oxygengenerated in 32 is diffused to the distributor 20 and to the functionalcells unit.

It is optional to provide an oxygen sensor (not shown in the figures)that detects the oxygen level and accordingly initiate or stop thecurrent between the electrodes using the microprocessor 36. The amountof oxygen generation is controllable in this way.

The amount of functional cells needed depends on physiologicalcharacteristics of the patient as well as the condition of the disease.Optionally, the gas unit is connected to several cell units as shown inFIG. 6, illustrating a medical system according to yet another exemplaryembodiment provided with a plurality of functional cells unit. MedicalSystem 200 comprises the same elements as in FIG. 1, however, more thanone distributer 20A and 20B as well as more than one functional cellsUnit 14A and 14B are provided. More cells units with their owndistributor of oxygen or a shared one can be employed in the system.

As mentioned herein before, the functional cell unit 14 is preferablyshaped as a disc-like member that has some degree of flexibility.Preferably, there are two adjacent compartments wherein the gas isdistributed between them.

Reference is now made to FIG. 7a illustrating a functional cell unit 14according to a preferred embodiment into which the distributor 20 isdistributing the gas. The gas can be distributed directly from a nozzleof the tube or through plurality holes 48, as an example. In thedisclosed preferred embodiment, functional cells 40 are being preferablyembedded within a matrix 44 in two disc shaped compartments 42A and 42Bfacing each other on both sides of the distributor 18. It should benoted that the cells can be also a tissue, like islets of Langerhans.The matrix in which the cells are embedded can be selected from a groupof materials such as alginate, collagen, a combination thereof, or anyother material in which oxygen as well as nutrients can diffuse within.

Each face of the disc-like compartment that faces the oppositecompartment as well as the sides of the compartments are covered by alayer of preferably silicone or hydrolyzed silicone 46 that allowsoxygen to pass through and get into the matrix in which the functionalcells are embedded. The opposite face of the disc-like compartment(outer sides) is covered with a layer 50 that is permeable to nutrientssuch as glucose, but is impermeable to immunologic factors that mightattack the cells like immune cells and immune globuloins (e.g. IgG).Layer 50 can be made of materials such as alginate or PEG or combinationwith other materials such as Teflon.

Such compartment should be in a thickness that is low enough to preventaggregation of the cells. In the case of Langerhans Islets, thethickness of the disc-like structure should be about between 200 and2,000 μm. If single cells are being utilized, the thickness of the unitcan be about 20 μm.

It is important to keep the surface area through which the oxygen passesto the cells as large as possible in order to ensure the viability ofthe cells.

Reference is now made to FIG. 7b illustrating for clarity, anothercompartment of the functional cells unit. As in the former embodiment,the faces that are exposed to the distributor of gas or oxygen from agenerator are covered with silicone layer 52 that allows the passage ofoxygen gas through the layer into the cell compartment. The oppositeface is covered with a layer 58 that is allowing nutrients to get intothe compartment. Within the compartment, a sponge-like material having aporous structure 56 is received onto which the functional cells 58 areimmobilized or captured. The porous structure 56 should have pores thatare sized so as to allow the functional cells to get inside and beentrapped within the pores.

Reference is now made to FIG. 7c illustrating for clarity, anotherembodiment of a compartment of the functional cells unit. As in theformer embodiments, the faces that are exposed to the distributor of gasor oxygen from a generator are covered with silicone layer 52 thatallows the passage of oxygen through the layer into the compartment. Theopposite face is covered with a layer 58 that is allowing nutrients toget into the compartment and allowing the hormone or other bio-materialsthat are produced by the functional cells, to diffuse outside. Thecompartment itself is built from a plurality of subunits built in ashape that could be similar to an egg carton. This structure ispreferable from the following reasons: the surface area that is occupiedin allowing the oxygen to pass through and reach the cells is relativelylarge and the thin areas 60 between the subunits render flexibility tothe whole structure. Within each subunit, it is provided functionalcells 58 or tissues 64 embedded within a matrix 62 such as alginate,collagen or a combination therein. In the preparation of the functionalcells unit, liquid or semi-liquid alginate, as an example, can be mixedwith the functional cells and poured to within the subunits so as tofill it. Another option is to accommodate a mass of matrix mixed withthe functional cells in a certain shape within each subunit.

The typical diameter of each subunit can be in the range of 10-2,500 μm.

Reference is now made to FIG. 7d illustrating for clarity reasons, yetanother compartment of the functional cells unit. As in the formerembodiments, the faces that are exposed to the distributor of gas oroxygen from a generator are covered with silicone layer 52 that allowsthe passage of oxygen through the layer into the compartment. Theopposite face is covered with a layer 58 that is allowing nutrients toget into the compartment and allowing the hormone to get out of thecompartment. Within the compartment, hair-like structures or innerprojections 64 are provided onto which the functional cells 58 arecaptured and the structure is strengthen. It is preferable that theprojections 64 will be made from materials such as silicone so as tofacilitate the transfer of oxygen to the functional cells.

Reference is now made to FIG. 8 illustrating a distributor according toanother preferred embodiment. In order to uniformly transfer the oxygento the functional cells that are embedded within a the structures asillustrated in FIGS. 7a-7d , the distributor of gas or oxygen can beprovided with means to better distribute the gas to the cells. This isan important feature of the present invention. The functional unit shownin FIG. 8 is the embodiment shown in FIG. 7a , however, thisdistribution of gas can be employed in any other embodiment that isshown as well as others. Distributor 18 is provided with plurality ofsmall tubes 66, each have a nozzle in a different area of the functionalcell unit 14. In this way, the availability of oxygen is similar for thecells in any of the areas of the cells unit, whether they are close tothe distributor or far from it.

It should be noted that the outer layer of the functional cells unit andother parts of the system contains materials that promotevascularization in the vicinity of the implanted system as well as othermaterials that should increase the immunedepression reaction of the bodyof the patient. For the purpose of inducing a dense vascular bed closeto the active surfaces of the functional cells unit, it is optional toadd bioactive agents such as Heparin, CSPG, HSPG, platelets derivatives,and mesenchymal stem cells. Reducing the local inflammation can beperformed by adding materials such as alpha-1 anti-trypsin, Anti-TNF-α(e.g. etanercept/Enbrel, pentoxifylline), and hMSC.

Each part of the system and the system as a whole can be manufactured byusing a 3D printer while keeping the material bio-compatible.

It is appreciated that certain features of the invention, which are, forclarity, described in the context of separate embodiments, may also beprovided in combination in a single embodiment. Conversely, variousfeatures of the invention, which are, for brevity, described in thecontext of a single embodiment, may also be provided separately or inany suitable sub combination.

Although the invention has been described in conjunction with specificembodiments thereof, it is evident that many alternatives, modificationsand variations will be apparent to those skilled in the art.Accordingly, it is intended to embrace all such alternatives,modifications and variations that fall within the spirit and broad scopeof the appended claims. All publications, patents and patentapplications mentioned in this specification are herein incorporated intheir entirety by reference into the specification, to the same extentas if each individual publication, patent or patent application wasspecifically and individually indicated to be incorporated herein byreference. In addition, citation or identification of any reference inthis application shall not be construed as an admission that suchreference is available as prior art to the present invention.

1.-20. (canceled)
 21. An implantable medical system comprising: a replenishment port configured to be implanted within a human body and configured to receive a gas comprising oxygen through a needle adapted to penetrate the replenishment port through skin of the human body; a gas unit configured to be implanted within the human body at a different location from the replenishment port, the gas unit comprising a pressurized reservoir configured to be replenished by the gas received in the replenishment port, wherein the gas unit is configured to maintain a pressure within the pressurized reservoir that is greater than one atmosphere; at least one functional cells unit configured to be implanted within the human body at a different location from the replenishment port and the gas unit, wherein the at least one functional cells unit contains a plurality of functional cells, and wherein the at least one functional cells unit is configured to receive the gas from the gas unit so as to maintain the functional cells in a viable condition; and a first unidirectional valve configured to be implanted within the human body at a location between the pressurized reservoir of the gas unit and the at least one functional cells unit, wherein the unidirectional valve is configured to regulate flow of the gas from the gas unit to the at least one functional cells unit.
 22. The implantable medical system of claim 21, further comprising at least one distributor configured to distribute the gas from the gas unit to the at least one functional cells unit.
 23. The implantable medical system of claim 21, further comprising a second unidirectional valve configured to be implanted within the human body at a location between the replenishment port and the pressurized reservoir of the gas unit, wherein the second unidirectional valve is configured to ensure the gas is solely transferred from the replenishment port to the pressurized reservoir.
 24. The implantable medical system of claim 21, wherein the functional cells are selected from a group comprising islets of Langerhans, adrenal cells, stem cells and genetic implantable cells.
 25. The implantable medical system of claim 21, wherein the at least one functional cells unit has one dimension that is relatively longer than other dimensions so as to render flexibility to the unit, and wherein the at least one functional cells unit is flexible enough so as to allow the at least one functional cells unit to partially follow the natural movements of organs of the human body that are adjacent to the at least one functional cells unit.
 26. The implantable medical system of claim 21, wherein the at least one functional cells unit is in a shape of a disc having a thickness in the range of between 1 mm and 8 mm and a diameter in the range of between 1 cm and 20 cm.
 27. The implantable medical system of claim 21, wherein the at least one functional cells unit comprises opposite positioned compartments of substantially the same dimensions, and wherein both compartments are configured to allow diffusion of oxygen to the functional cells inside the at least one functional cells unit.
 28. The implantable medical system of claim 27, wherein the compartments are disc-like and have a thickness in the range of between 20 μm and 2,000 μm.
 29. The implantable medical system of claim 21, wherein at least a portion of the at least one functional cells unit is covered with a layer that facilitates transfer of oxygen.
 30. The implantable medical system of claim 29, wherein the at least a portion of the at least one functional cells unit includes a portion of the at least one functional cells unit that faces the gas unit.
 31. The implantable medical system of claim 21, wherein at least one outer side of the at least one functional cells unit is covered with a layer that is (a) permeable to nutrients that may be consumed by functional cells, (b) permeable to bio-materials that may be produced by the functional cells, and (c) impermeable to immunologic factors and oxygen.
 32. The implantable medical system of claim 21, wherein the functional cells are embedded in a matrix within the at least one functional cells unit.
 33. The implantable medical system of claim 32, wherein the matrix includes a material selected from a group comprising alginate, collagen, and combinations thereof.
 34. The implantable medical system of claim 21, wherein the functional cells in the at least one functional cells unit are trapped within a porous structure.
 35. The implantable medical system of claim 21, wherein the at least one functional cells unit comprises a plurality of subunits provided with functional cells embedded in a matrix, wherein each of the plurality of subunits is configured to allow diffusion of oxygen to the functional cells.
 36. The implantable medical system of claim 35, wherein the diameter of each subunit is in a range of between 10 μm and 2,500 μm.
 37. The implantable medical system of claim 21, wherein the at least one functional cells unit comprises inner projections configured to allow the functional cells to be captured thereon.
 38. The implantable medical system of claim 37, wherein the inner projections are configured to facilitate transfer of oxygen to the functional cells.
 39. The implantable medical system of claim 38, wherein the inner projections comprise silicon. 